Cognitive impairment in multiple sclerosis can be predicted by imaging early in the disease

Institute of Neurology, University College London, Queen Square, London, UK.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 09/2008; 79(8):955-8. DOI: 10.1136/jnnp.2007.138685
Source: PubMed


Cognitive impairment is common in multiple sclerosis (MS) and adds significantly to the burden of the disease. The ability to predict future cognitive impairment from imaging obtained at disease onset has not been investigated.
62 patients imaged within 3 months of a clinically isolated syndrome were assessed neuropsychologically 7 years later. Baseline and periodic MRI measures of lesions, atrophy and normal-appearing white and grey matter were regressed against neuropsychological scores to explore the best predictors of cognitive outcome.
28 patients had developed clinically definite MS at follow-up and a further nine met revised McDonald criteria for MS. Deficits in speed of information processing and executive function were the most common abnormalities. Poor performance correlated with high anxiety ratings. Baseline T(1) lesion metrics predicted executive deficits, and new T(2) lesions at the 3-month follow-up predicted slowed information processing. An increase in myo-inositol concentration in normal-appearing white matter over the first 3 years was associated with poor executive function.
MRI variables obtained at the onset of a clinically isolated syndrome can predict future development of cognitive abnormalities. Our findings may have implications in monitoring and treating patients.

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    • "In particular, MRS allows quantification not only of N-acetyl-aspartate (NAA), which is a marker of neuronal health and integrity [Moffett et al., 2007], but also of other important metabolites , such as myo-inositol (Ins) and choline (Cho), which reflect glial proliferation (and activation) and membrane turnover associated with inflammation [Bitsch et al., 1999], respectively. Abnormal concentrations of metabolites, including NAA and Ins, have been reported in the brain [Chard et al., 2002; Sastre-Garriga et al., 2005; Tiberio et al., 2006] and spinal cord [Ciccarelli et al., 2007; Marliani et al., 2007, 2010] of patients with MS when compared with controls, and are associated with motor disability [Chard et al., 2002; Sastre-Garriga et al., 2005] and cognitive impairment [Summers et al., 2008]. Many spectroscopy studies have investigated relatively large volumes in the central nervous system (CNS) using chemical-shift imaging (CSI), which permits excitation of a large spectroscopic volume located on axial slices and collects the spectral data from many voxels [Chard et al., 2002; Sastre-Garriga et al., 2005]. "
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    ABSTRACT: We characterized metabolic changes along the cortico-spinal tract (CST) in multiple sclerosis (MS) patients using a novel application of chemical shift imaging (CSI) and considering the spatial variation of metabolite levels. Thirteen relapsing-remitting (RR) and 13 primary-progressive (PP) MS patients and 16 controls underwent (1) H-MR CSI, which was applied to coronal-oblique scans to sample the entire CST. The concentrations of the main metabolites, i.e., N-acetyl-aspartate, myo-Inositol (Ins), choline containing compounds (Cho) and creatine and phosphocreatine (Cr), were calculated within voxels placed in regions where the CST is located, from cerebral peduncle to corona radiata. Differences in metabolite concentrations between groups and associations between metabolite concentrations and disability were investigated, allowing for the spatial variability of metabolite concentrations in the statistical model. RRMS patients showed higher CST Cho concentration than controls, and higher CST Ins concentration than PPMS, suggesting greater inflammation and glial proliferation in the RR than in the PP course. In RRMS, a significant, albeit modest, association between greater Ins concentration and greater disability suggested that gliosis may be relevant to disability. In PPMS, lower CST Cho and Cr concentrations correlated with greater disability, suggesting that in the progressive stage of the disease, inflammation declines and energy metabolism reduces. Attention to the spatial variation of metabolite concentrations made it possible to detect in patients a greater increase in Cr concentration towards the superior voxels as compared to controls and a stronger association between Cho and disability, suggesting that this step improves our ability to identify clinically relevant metabolic changes. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Human Brain Mapping 03/2014; 35(3). DOI:10.1002/hbm.22229 · 5.97 Impact Factor
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    • "Feinstein et al. [7], Summer et al. [22], and Audoin et al. [23] found reduced information processing speed in CIS. Nilsson et al. [24] and Summers et al. [22] found changes in executive function and processing speed performance. Glanz et al. [6] found impairment in working memory, processing speed, and verbal memory. "
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    ABSTRACT: Objective: To investigate cognitive impairment, to assess optical nerve axonal loss, and to determinate whether there is correlation between optical nerve axonal loss and cognition impairment in Clinically Isolated Syndrome (CIS). Methods: Fifteen CIS patients and 15 controls were submitted to Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial Addition, Digit Span, verbal fluency, stroop color, D2, and Digit Symbol tests. CIS patients were evaluated by optical coherence tomography (OCT) (23 eyes). Results: CIS patients had worse performance in Paced Auditory Serial Addition Test (PASAT) 2 seconds (P=0.009) and fluency tests (P=0.0038). Optical nerve axonal loss was found more frequently in eyes with previous optic neuritis (ON) (85.7%) than in those without previous ON (21.7%) (P=0.0146). There were no significant correlations between optical nerve axonal loss and cognitive findings. Conclusions: CIS patients had worse cognitive performance than controls. OCT can detect axonal loss resulting from optical neuritis and subclinical axonal loss in eyes without previous optical neuritis. Optical nerve axonal loss was not correlated with cognition.
    Clinical neurology and neurosurgery 11/2012; 115(7). DOI:10.1016/j.clineuro.2012.10.025 · 1.13 Impact Factor
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    • "In patients with either RRMS or SPMS, the increase in T1 lesion volume (LV) over time correlates significantly with progressive cerebral atrophy and the change in EDSS score (Sailer et al., 2001; Truyen et al., 1996). Moreover, in patients with CIS, baseline T1 hypointense lesion number and volume are strong predictors of the severity of executive dysfunction (Summers et al., 2008). "

    Neuroimaging - Clinical Applications, 03/2012; , ISBN: 978-953-51-0200-7
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